The long-term objective of this project is to define the relationship between epidermal cell proliferation and differentiation. We propose to study the effect of selected drugs and other agents of primary epidermal cell culture function. We define function as proliferation and differentiation. We propose for the oncoming year: 1) to continue our studies of 3H-histidine and leucine labeling of epidermal cell cultures. We will continue our investigation of the cAMP effects; in addition we propose to study the TPA & Triamcinolone Acetonide effects on differentiation. 2) We shall continue our studies of shifts of PO2 on epidermal cell proliferation & cell cycle. We propose to see if PO2 shifts change alpha-helical polypeptide cross-linking. 3) We shall continue our collaborations with Dr. Ziboh and our study of arachidonic acid metabolites in epidermal cells, and with Drs. David Bickers and Hasan Mukhtar on mixed function oxidases in the epidermal cell cultures. 4) If no problems arise between Hoffman LaRoche (Supplier of 13-cis retinoic acid and Ro 10-9359) and the University of Michigan) we shall continue our studies of Ro 10-9359, 13-cis retinoic acid and other retinoids on epidermal cell function. 5) We shall continue to vary culture conditions to establish psoriatic cell cultures. The results of the proposed investigations can yield information contributing to an understanding of epidermal cell control mechanisms and can result in improved therapies for the treatment of cell proliferation-differentiation disorders, specifically, psoriasis.